uPA/PAI-1 ratios distinguish benign prostatic hyperplasia and prostate cancer

Urokinase plasminogen activator (uPA) and its inhibitor type 1 (PAI-1) are associated with tumour metabolism and are widely considered to be informative for the identification of cancer. We have analysed prostate tissue resections from patients with prostate cancer (PCa) and with benign prostatic hyperplasia (BPH) for protein levels of uPA and PAI-1, and searched for distinctions between these two clinical manifestations.

Prostate tissue was deep frozen in liquid N2 and homogenized in a stainless steel punch homogenizer. The tissue powder was extracted with a pH 8.5 TRIS/Triton X-100 buffer, and the extract analysed by FEMTELLE assay to generate uPA and PAI-1 readings in ng/mg protein. The uPA/PAI-1 ratio was calculated for each sample, and the mean ratios for the two diagnostic groups were compared.

The concentration of uPA (mean ± SD) was found to be 0.19 ± 0.04 ng/mg protein (range 0.05-0.72 ng/mg) and 0.15 ± 0.02 ng/mg protein (range 0.03-0.78 ng/mg) in PCa and BPH samples, respectively. The concentration of PAI-1 was found to be 4.93 ± 0.90 ng/mg (range 1.10-11.80 ng/mg) and 5.87 ± 0.70 ng/mg (range 0.2-25.0 ng/mg) in PCa and BPH samples, respectively. A consistent finding being that PAI-1 concentrations exceed uPA concentrations by far giving rise to characteristic uPA/PAI-1 ratios. In BPH samples, there was a trend of PAI-1 to increase with uPA content, while in PCa samples, PAI-1 remained fairly constant. The mean uPA/PAI-1 ratio in PCa samples was found to be 0.06 ± 0.01 and was significantly higher than in BPH samples where the mean uPA/PAI-1 ratio was 0.03 ± 0.003 (p = 0.0028). R(2) = 0.1389.

Using a contingent of 62 patients of which 46 were BPH and 16 were PCa, we report definitive concentrations of uPA and PAI-1 in tumour tissue extracts and show that the uPA/PAI-1 ratio emerges as a candidate marker to distinguish between BPH and PCa.